Herman A.W. Hazewinkel, DVM, PhD, DECVS, DECVCN
Dept. Clinical Sciences of Companion Animals, Utrecht University
The practising veterinarian is often confronted with dogs and cats of the same breed, and sometimes even from the same breeder, with corresponding complains. Following Petterson, who stated that whenever animals of the same breed have the same complains at the same anatomical place, the disease has to be considered hereditary. He added to that statement that there should also be the same chromosomal defect, but since of most current hereditary diseases of the skeleton the molecular genetic background has not been elucidated we better limit to the first part of this statement. Often more than one gene is involved in hereditary skeletal diseases although in some cases major genes are involved (i.e., one or some of the genes have more influence on the occurrence of the disease than others), often the hereditary pattern is recessive, and often the disease is multifactorial (i.e., environmental influences are of importance or necessary to express the genotype into the phenotype). Some of the hereditary diseases are present at birth (i.e., constitutional), whereas other hereditary diseases become manifest during growth of even later in life (i.e., acquired hereditary diseases). Especially the latter is confusing for owners and breeders, but the informed veterinarian can clarify and council the breeder of the effected dog and its owners. Often the hereditary skeletal disease comes alone, but in some cases it might be associated with diseases of other organ systems. In the following section, different examples of the variety of skeletal diseases frequently diagnosed in the veterinary practice will be given.
At the age of 3 months it becomes obvious that the dog is not growing like its littermates. The front and rear legs stay to short for the length of the dog and the size of its head. This dys-proportional growth can be made objective by comparing radiographs of the antebrachium with that of one of the littermates. At the distal growth plate of the ulna, an abnormal alignment (differing from the normally present V-shape) can be noticed. In some cases an abnormal configuration of the elbow joint can be seen, i.e., a lateral luxation of the radial head together with a too short but straight ulna. From the anamnesis can be learned that this abnormality has been noticed before in litters of this or related bitches. The skeletal disease is recessive. It has been described to occur in conjunction with severe retinal dysplasia in the U.S.A. (Carrig et al, 1988), whereas in The Netherlands several cases with chondrodysplasia never demonstrated retinal dysplasia leading to the conclusion that both diseases may occur in the same individual due to the fact the genes coding for each disease are closely connected on the same chromosome. In the Alaskan Malamute a similar manifestation of chondrodysplasia can occur (Fletch et al, 1975), also a simple autosomal recessive hereditary disease with variable phenotypic expression and may and may not occur together with haematological abnormalities. Although similar diseases are described in Great Pyrenees, Norwegian Elkhound, Samoyed and can be seen in other breeds as well, this does not imply that the cause of the chondrodysplasia is related. The shortening of the legs in Dachshunds is more severe and grouped under the achondroplasias, although the typical (FGFR3) mutation which goes with achondrodysplasia in dogs of many other breeds, is not mutated in Dachshunds (Martines et al, 1998)
Craniomandibular osteopathy (CMO)
This disease is characterized by new bone formation affecting the flat bones of the head, i.e., the mandible, the cranium and also the tympanic bullae, while the mandibular joint is free of new bone. This disease starts with reluctance to play with balls and to eat and eventually to open the mouth. The disease starts at 4-5 months of age and is not seen after maturity of the dog. Mandibles are painful on palpation and a radiograph can reveal the periosteal new bone formation. In the beginning this can be spur-like, whereas it can grow to a large extend. When the mandibular joint is not hundred by bone bridges, the therapy is limited to NSAID (plus corticosteroids) and good nursing. In some dogs suffering from hypertrophic osteodystrophy, periosteal new bone formation can be noticed on the mandibles as well. It should be realized that bones can only react in a limited amount of ways: either more bone or less. This periosteal bone formation can be rather non-specific, but since it is seen in young dogs of a certain (limited amount of) breeds in only the flat bones of the head we can consider it as a hereditary disease. CMO has been demonstrated to be an autosomal recessive trait in West Highland White Terriers, as it is most probably also in related Terriers including Cairn, Scottish and Border Terriers (LaFond et al 1998, Padgett et al 1986).
Although patella luxation can occur after traumatic rupture of the retinaculum and can be iatrogenic induced after arthrotomy of the stifle joint, most patella luxations are due to a fault alignment in the stifle joint. The primary abnormality can originate from morphological changes in the hip joint, or from a relative rotation of the tibial tuberosity relative to the femur. In all cases the patella has the tendency to luxate in medial and/or lateral direction. Graded by Putnam and many others, it can occur after manual luxation or spontaneously, can be repositioned spontaneously, manually or not at all either to the medial or lateral direction.
In addition patella luxation can be the cause of abnormal growth of the distal growth plate of the femur (genu valgum syndrome). In particular toy breeds are at risk (Priester 1972), as well as Flatcoated retrievers, Fox and Jack Russell Terriers, Kooikerhondje and cats of different breeds (Meutstege, 2003). The disease may vary from staying unnoticed, till refusal to jump and inability to bear weight.
Although high calcium intake is considered as an important dietary factor for many multifactorial skeletal diseases, Nap (1993) demonstrated that a high calcium intake in miniature poodles did not induced the disease.
Incongruity of the elbow joint due to a radial overgrowth is seen in Bernese Mountain Dogs in 80% of the dogs with osteoarthrosis in the elbow joint. In a survey of a large group of Bernese Mountain dogs this type of incongruity was seen in all cases with elbow lameness in conjunction with a fragmented coronoid process (Ubbink et al, 1999). Population analyses revealed that the disease was introduced right after WW II by a limited number of founding fathers and from there introduced in the breed.
Fragmented coronoid process of the medial aspect of the ulna is seen in many breeds and in large percentages, up till 50% of the screened population (Svenson et al, 1997, Ubbink et al, 1999). The heritability estimates are between 0.24-0.43 for Bernese Mountain Dogs, for Labradors 0.77 and for Golden Retrievers 0.45 (Guthrie and Pidduck, 1990). For Retrievers, these figures are for OCD plus FCP, and thus found to be polygenetic in addition to multifactorial (Padgett et al, 1995).
The ununited anconeal process was called elbow dysplasia, long before the above entities were covered by this term as well (Corley et al, 1965). It is seen in chondrodystrophic breeds (like Bassets) and as part of elbow incongruity in certain breeds (German Shepherd, St Bernard) as well as due to nutrition induced or traumatic radius curvus syndrome (Hazewinkel, 1998).
Cluster analysis, using computerized programmes containing all pedigree of the investigated population, reveals histograms. Each bar represents a group of related dogs with 1/8 of the genome in common. All dogs were screened radiologically for FCP. The black areas in the bars represent those dogs found positive for FCP; in the affected groups this is 27-50% of the investigated dogs. These groups of dogs are spread over the country, but are quit related, as can be seen from the horizontal connection lines. Not affected groups are less related. Although this method does not show the inheritance pattern, it is proven to be an effective method for persuading kennel clubs to take measurements like obligation of screening before breeding.
Morbus Calvé Legg Perthes
Avascular femoral head necrosis is seen in young small breed terriers of both sexes, although we have seen prevalence in male Yorkshire terriers. The diseases is characterised by a painful lameness of one hind leg (in extraordinary cases the disease is bilateral) with radiographically a dark area in the femoral epiphysis, which will eventually lead to collapse of the femoral head. In West Highland White and Manchester Terriers analysis of pedigrees revealed a simple autosomal recessive trait, although possibly multifactorial (Wallin, 1986, Vasseur et al, 1989). This disease is also diagnosed in Miniature pinschers, toy poodles and other miniature dogs. A slow skeletal maturation with obliteration of a vulnerable blood vessel, which nourishes the epiphysis, crossing the joint between joint capsule and femoral head, is hold responsible for the necrosis of the femoral head.
OCD of the hock joint
In young dogs of medium breeds, in particular Labradors and Rottweilers, lameness of one or both hind legs can be seen starting at the age of 6 months. The tibiotarsal joint is swollen, crepitation on passive movements and painful on hyperextension. On the radiograph, an indentation can be noticed on the mediolateral view of the ridge of the talus. At the AP view, the skyline of the ridge can make a cartilage flap visible. In Rottweilers this can be the medial or lateral ridge, in Labradors this is almost without exception the medial ridge. Computerized cluster analysis of pedigree of Labrador retrievers demonstrated the heritability of the disease in this breed (Hazewinkel & Ubbink, 2004).
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8. Ubbink GJ, Hazewinkel HAW, van den Broek J, Rothuizen J. Familial clustering and risk analysis for FCP and elbow joint incongruity in Bernese Mountain Dogs in The Netherlands AJVR 60, 1082-1087, 1999
9. Ubbink GJ, van den Broek J, Hazewinkel HAW, Wolvekamp WTC, Rothuizen J. Prediction of the genetic risk for fragmented coronoid process in Labrador retrievers. Vet Rec. 147, 149-152, 2000
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16. Hazewinkel HAW, Ubbink G. Pedigree analysis of Labradors with OCD of the talocrural joint, in press